UA59417C2 - Сполуки піперидиніламінометильних трифлуорометильних циклічних етерів, фармацевтична композиція (варіанти) та спосіб лікування (варіанти) - Google Patents

Сполуки піперидиніламінометильних трифлуорометильних циклічних етерів, фармацевтична композиція (варіанти) та спосіб лікування (варіанти) Download PDF

Info

Publication number: UA59417C2
Authority: UA; Ukraine
Prior art keywords: methoxy; disorders; methyl; trifluoromethyl; dihydroisobenzofuran
Prior art date: 1997-11-19

Application number

UA2000042374A

Other languages

English (en)

Russian (ru)

Ukrainian (uk)

Inventor

Куніо Сатаке

Original Assignee

Файзер Інк.

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-11-19

Filing date

1998-10-26

Publication date

2003-09-15

1998-10-26 Application filed by Файзер Інк. filed Critical Файзер Інк.

2003-09-15 Publication of UA59417C2 publication Critical patent/UA59417C2/uk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 145
-1 trifluoromethyl cyclic ethers Chemical class 0.000 title abstract description 30
239000005557 antagonist Substances 0.000 title description 8
239000000126 substance Substances 0.000 title description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 44
208000035475 disorder Diseases 0.000 claims abstract description 40
150000003839 salts Chemical class 0.000 claims abstract description 35
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
239000001257 hydrogen Substances 0.000 claims abstract description 30
206010047700 Vomiting Diseases 0.000 claims abstract description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
206010046543 Urinary incontinence Diseases 0.000 claims abstract description 7
230000000172 allergic effect Effects 0.000 claims abstract description 6
208000010668 atopic eczema Diseases 0.000 claims abstract description 6
208000015114 central nervous system disease Diseases 0.000 claims abstract description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
125000001475 halogen functional group Chemical group 0.000 claims abstract 4
125000000217 alkyl group Chemical group 0.000 claims description 31
238000000034 method Methods 0.000 claims description 27
208000019901 Anxiety disease Diseases 0.000 claims description 21
QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 claims description 16
241000124008 Mammalia Species 0.000 claims description 16
102100024304 Protachykinin-1 Human genes 0.000 claims description 16
101800003906 Substance P Proteins 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 15
150000002367 halogens Chemical class 0.000 claims description 14
208000024714 major depressive disease Diseases 0.000 claims description 14
230000036506 anxiety Effects 0.000 claims description 12
208000002193 Pain Diseases 0.000 claims description 11
230000008673 vomiting Effects 0.000 claims description 11
208000010877 cognitive disease Diseases 0.000 claims description 9
208000020925 Bipolar disease Diseases 0.000 claims description 8
208000019695 Migraine disease Diseases 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
206010027599 migraine Diseases 0.000 claims description 8
208000016285 Movement disease Diseases 0.000 claims description 7
206010041303 Solar dermatitis Diseases 0.000 claims description 7
230000009931 harmful effect Effects 0.000 claims description 7
208000027866 inflammatory disease Diseases 0.000 claims description 7
201000000980 schizophrenia Diseases 0.000 claims description 7
201000001880 Sexual dysfunction Diseases 0.000 claims description 6
210000001035 gastrointestinal tract Anatomy 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
231100000872 sexual dysfunction Toxicity 0.000 claims description 6
208000011117 substance-related disease Diseases 0.000 claims description 6
230000006459 vascular development Effects 0.000 claims description 6
208000013200 Stress disease Diseases 0.000 claims description 5
230000003042 antagnostic effect Effects 0.000 claims description 5
210000003169 central nervous system Anatomy 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
NBUDNQJPOCYIIN-UHFFFAOYSA-N 5-methoxy-1-(trifluoromethyl)-1,3-dihydro-2-benzofuran Chemical compound COC1=CC=C2C(C(F)(F)F)OCC2=C1 NBUDNQJPOCYIIN-UHFFFAOYSA-N 0.000 claims description 4
ARZVJUKNXGNLEF-UHFFFAOYSA-N 6-methoxy-3,3-bis(trifluoromethyl)-1h-2-benzofuran Chemical compound COC1=CC=C2C(C(F)(F)F)(C(F)(F)F)OCC2=C1 ARZVJUKNXGNLEF-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
FGGKIMGMRFUCLN-UHFFFAOYSA-N 6-methoxy-3-methyl-3-(trifluoromethyl)-1h-2-benzofuran Chemical compound COC1=CC=C2C(C(F)(F)F)(C)OCC2=C1 FGGKIMGMRFUCLN-UHFFFAOYSA-N 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
230000002265 prevention Effects 0.000 claims description 3
XIRBHTNKLIOEGN-UHFFFAOYSA-N 6-methoxy-3-phenyl-3-(trifluoromethyl)-1h-2-benzofuran Chemical compound C=1C(OC)=CC=C2C=1COC2(C(F)(F)F)C1=CC=CC=C1 XIRBHTNKLIOEGN-UHFFFAOYSA-N 0.000 claims description 2
238000012876 topography Methods 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 5
238000002360 preparation method Methods 0.000 abstract description 3
239000002260 anti-inflammatory agent Substances 0.000 abstract description 2
229940121363 anti-inflammatory agent Drugs 0.000 abstract description 2
241000590002 Helicobacter pylori Species 0.000 abstract 1
206010042496 Sunburn Diseases 0.000 abstract 1
230000002411 adverse Effects 0.000 abstract 1
229940035676 analgesics Drugs 0.000 abstract 1
230000033115 angiogenesis Effects 0.000 abstract 1
239000000730 antalgic agent Substances 0.000 abstract 1
229940037467 helicobacter pylori Drugs 0.000 abstract 1
208000014001 urinary system disease Diseases 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 77
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 64
239000000243 solution Substances 0.000 description 46
239000000203 mixture Substances 0.000 description 41
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 34
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
238000005481 NMR spectroscopy Methods 0.000 description 27
239000011541 reaction mixture Substances 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 21
229910052943 magnesium sulfate Inorganic materials 0.000 description 20
235000019341 magnesium sulphate Nutrition 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
239000000284 extract Substances 0.000 description 18
238000003756 stirring Methods 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
239000012043 crude product Substances 0.000 description 17
229910052757 nitrogen Inorganic materials 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
238000004519 manufacturing process Methods 0.000 description 13
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
239000012267 brine Substances 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
239000013078 crystal Substances 0.000 description 11
239000003921 oil Substances 0.000 description 11
235000019198 oils Nutrition 0.000 description 11
239000002904 solvent Substances 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
239000012230 colorless oil Substances 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000004587 chromatography analysis Methods 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
150000001412 amines Chemical class 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
238000000746 purification Methods 0.000 description 8
239000007787 solid Substances 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
239000002585 base Substances 0.000 description 7
150000002009 diols Chemical class 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000010410 layer Substances 0.000 description 7
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 6
239000012442 inert solvent Substances 0.000 description 6
210000001589 microsome Anatomy 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
238000010898 silica gel chromatography Methods 0.000 description 6
241000282412 Homo Species 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000000463 material Substances 0.000 description 5
SFLGSKRGOWRGBR-UHFFFAOYSA-N phthalane Chemical group C1=CC=C2COCC2=C1 SFLGSKRGOWRGBR-UHFFFAOYSA-N 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 5
BGKYIHZTAGIZDV-UHFFFAOYSA-N 2-[(2-bromo-5-methoxyphenyl)methoxy]oxane Chemical compound COC1=CC=C(Br)C(COC2OCCCC2)=C1 BGKYIHZTAGIZDV-UHFFFAOYSA-N 0.000 description 4
241000283725 Bos Species 0.000 description 4
241000699694 Gerbillinae Species 0.000 description 4
230000010933 acylation Effects 0.000 description 4
238000005917 acylation reaction Methods 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000012458 free base Substances 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
238000011534 incubation Methods 0.000 description 4
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000000758 substrate Substances 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
238000002424 x-ray crystallography Methods 0.000 description 4
AIDOYMJRTHZJOH-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoro-2-[2-(hydroxymethyl)-4-methoxyphenyl]propan-2-ol Chemical compound COC1=CC=C(C(O)(C(F)(F)F)C(F)(F)F)C(CO)=C1 AIDOYMJRTHZJOH-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
239000004471 Glycine Substances 0.000 description 3
208000032843 Hemorrhage Diseases 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
102000003141 Tachykinin Human genes 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
230000003110 anti-inflammatory effect Effects 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000000872 buffer Substances 0.000 description 3
235000017663 capsaicin Nutrition 0.000 description 3
229960002504 capsaicin Drugs 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 3
238000001914 filtration Methods 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
230000004060 metabolic process Effects 0.000 description 3
239000002674 ointment Substances 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
238000005932 reductive alkylation reaction Methods 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
108060008037 tachykinin Proteins 0.000 description 3
238000012360 testing method Methods 0.000 description 3
DJBCDJIBMLMRIL-UHFFFAOYSA-N 1,1,1-trifluoro-2-[4-methoxy-2-[2-(oxan-2-yloxy)ethyl]phenyl]propan-2-ol Chemical compound COC1=CC=C(C(C)(O)C(F)(F)F)C(CCOC2OCCCC2)=C1 DJBCDJIBMLMRIL-UHFFFAOYSA-N 0.000 description 2
FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 2
XVDBQNMBIOIJLX-UHFFFAOYSA-N 1-bromo-2-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(Br)C(CCl)=C1 XVDBQNMBIOIJLX-UHFFFAOYSA-N 0.000 description 2
RRLUBXRGQOSEGO-UHFFFAOYSA-N 2,2,2-trifluoro-1-[2-(hydroxymethyl)-4-methoxyphenyl]ethanol Chemical compound COC1=CC=C(C(O)C(F)(F)F)C(CO)=C1 RRLUBXRGQOSEGO-UHFFFAOYSA-N 0.000 description 2
MSJDVAUSKYFUNN-UHFFFAOYSA-N 2,2,2-trifluoro-1-[4-methoxy-2-(oxan-2-yloxymethyl)phenyl]ethanol Chemical compound COC1=CC=C(C(O)C(F)(F)F)C(COC2OCCCC2)=C1 MSJDVAUSKYFUNN-UHFFFAOYSA-N 0.000 description 2
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
DENHQXCFRKDVGB-UHFFFAOYSA-N 2-[2-(2-bromo-5-methoxyphenyl)ethoxy]oxane Chemical compound COC1=CC=C(Br)C(CCOC2OCCCC2)=C1 DENHQXCFRKDVGB-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
206010027654 Allergic conditions Diseases 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 2
108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
101100534115 Drosophila melanogaster Snup gene Proteins 0.000 description 2
241000196324 Embryophyta Species 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
108010044467 Isoenzymes Proteins 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
150000001263 acyl chlorides Chemical class 0.000 description 2
230000003474 anti-emetic effect Effects 0.000 description 2
229940098773 bovine serum albumin Drugs 0.000 description 2
150000001728 carbonyl compounds Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
229960004316 cisplatin Drugs 0.000 description 2
239000006071 cream Substances 0.000 description 2
239000010779 crude oil Substances 0.000 description 2
125000004093 cyano group Chemical group *C#N 0.000 description 2
SGTNSNPWRIOYBX-HHHXNRCGSA-N dexverapamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCC[C@@](C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-HHHXNRCGSA-N 0.000 description 2
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000000945 filler Substances 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
230000022244 formylation Effects 0.000 description 2
238000006170 formylation reaction Methods 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
230000026030 halogenation Effects 0.000 description 2
238000005658 halogenation reaction Methods 0.000 description 2
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
239000005457 ice water Substances 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007928 intraperitoneal injection Substances 0.000 description 2
235000015110 jellies Nutrition 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
210000001853 liver microsome Anatomy 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000001465 metallisation Methods 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 2
XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
208000004296 neuralgia Diseases 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
150000003053 piperidines Chemical class 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
239000012047 saturated solution Substances 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
210000000626 ureter Anatomy 0.000 description 2
NRDAKNCVXNJCGB-UHFFFAOYSA-N (2-bromo-5-methoxyphenyl)methanol Chemical compound COC1=CC=C(Br)C(CO)=C1 NRDAKNCVXNJCGB-UHFFFAOYSA-N 0.000 description 1
MRXDGVXSWIXTQL-HYHFHBMOSA-N (2s)-2-[[(1s)-1-(2-amino-1,4,5,6-tetrahydropyrimidin-6-yl)-2-[[(2s)-4-methyl-1-oxo-1-[[(2s)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]amino]-2-oxoethyl]carbamoylamino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C=O)C1NC(N)=NCC1)C(O)=O)C1=CC=CC=C1 MRXDGVXSWIXTQL-HYHFHBMOSA-N 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
WAYCQEPIQNTRDJ-UHFFFAOYSA-N 1,3-dihydro-2-benzofuran-5-carbaldehyde Chemical compound O=CC1=CC=C2COCC2=C1 WAYCQEPIQNTRDJ-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
VGISFWWEOGVMED-UHFFFAOYSA-N 1-(chloromethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CCl)=C1 VGISFWWEOGVMED-UHFFFAOYSA-N 0.000 description 1
RHQQHZQUAMFINJ-GKWSUJDHSA-N 1-[(3s,5s,8s,9s,10s,11s,13s,14s,17s)-3,11-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-hydroxyethanone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CC[C@H]21 RHQQHZQUAMFINJ-GKWSUJDHSA-N 0.000 description 1
KZJRKRQSDZGHEC-UHFFFAOYSA-N 2,2,2-trifluoro-1-phenylethanone Chemical compound FC(F)(F)C(=O)C1=CC=CC=C1 KZJRKRQSDZGHEC-UHFFFAOYSA-N 0.000 description 1
229940087189 2,2,2-trifluoroacetophenone Drugs 0.000 description 1
NCVWURWGRQEAAU-UHFFFAOYSA-N 2-(2-bromo-5-methoxyphenyl)ethanol Chemical compound COC1=CC=C(Br)C(CCO)=C1 NCVWURWGRQEAAU-UHFFFAOYSA-N 0.000 description 1
UTMIEQASUFFADK-UHFFFAOYSA-N 3,3,3-trifluoropropanal Chemical compound FC(F)(F)CC=O UTMIEQASUFFADK-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
229940113081 5 Hydroxytryptamine 3 receptor antagonist Drugs 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
108010001478 Bacitracin Proteins 0.000 description 1
108010017384 Blood Proteins Proteins 0.000 description 1
102000004506 Blood Proteins Human genes 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
208000009079 Bronchial Spasm Diseases 0.000 description 1
208000014181 Bronchial disease Diseases 0.000 description 1
206010006482 Bronchospasm Diseases 0.000 description 1
COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
241000700198 Cavia Species 0.000 description 1
208000000094 Chronic Pain Diseases 0.000 description 1
OLVPQBGMUGIKIW-UHFFFAOYSA-N Chymostatin Natural products C=1C=CC=CC=1CC(C=O)NC(=O)C(C(C)CC)NC(=O)C(C1NC(N)=NCC1)NC(=O)NC(C(O)=O)CC1=CC=CC=C1 OLVPQBGMUGIKIW-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
208000012661 Dyskinesia Diseases 0.000 description 1
208000030814 Eating disease Diseases 0.000 description 1
208000019454 Feeding and Eating disease Diseases 0.000 description 1
238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
208000027601 Inner ear disease Diseases 0.000 description 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
239000004367 Lipase Substances 0.000 description 1
102000004882 Lipase Human genes 0.000 description 1
108090001060 Lipase Proteins 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
206010028347 Muscle twitching Diseases 0.000 description 1
XJLXINKUBYWONI-NNYOXOHSSA-N NADP zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
241000588653 Neisseria Species 0.000 description 1
208000028389 Nerve injury Diseases 0.000 description 1
102000002002 Neurokinin-1 Receptors Human genes 0.000 description 1
108010040718 Neurokinin-1 Receptors Proteins 0.000 description 1
102000003797 Neuropeptides Human genes 0.000 description 1
108090000189 Neuropeptides Proteins 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
108091034117 Oligonucleotide Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
ZPHBZEQOLSRPAK-UHFFFAOYSA-N Phosphoramidon Natural products C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O ZPHBZEQOLSRPAK-UHFFFAOYSA-N 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
229920002873 Polyethylenimine Polymers 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
206010039966 Senile dementia Diseases 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
241000282887 Suidae Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
206010043118 Tardive Dyskinesia Diseases 0.000 description 1
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
208000000323 Tourette Syndrome Diseases 0.000 description 1
208000016620 Tourette disease Diseases 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
206010047141 Vasodilatation Diseases 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
AEKVTYPHESXBID-GFCCVEGCSA-N [(1r)-1-methyl-1-(trifluoromethyl)-3,4-dihydroisochromen-6-yl] acetate Chemical compound C=1([C@](OCC2)(C)C(F)(F)F)C2=CC(OC(=O)C)=CC=1 AEKVTYPHESXBID-GFCCVEGCSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
238000000862 absorption spectrum Methods 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
208000005298 acute pain Diseases 0.000 description 1
150000001265 acyl fluorides Chemical class 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000001413 amino acids Chemical group 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000002111 antiemetic agent Substances 0.000 description 1
229940125683 antiemetic agent Drugs 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 description 1
229960003071 bacitracin Drugs 0.000 description 1
229930184125 bacitracin Natural products 0.000 description 1
CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
230000027455 binding Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
208000028683 bipolar I disease Diseases 0.000 description 1
239000001045 blue dye Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical class B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
229960003563 calcium carbonate Drugs 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
108010086192 chymostatin Proteins 0.000 description 1
238000010549 co-Evaporation Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
230000006835 compression Effects 0.000 description 1
238000007906 compression Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
239000013256 coordination polymer Substances 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
239000013058 crude material Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
208000026725 cyclothymic disease Diseases 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
CDHICTNQMQYRSM-UHFFFAOYSA-N di(propan-2-yl)alumane Chemical compound CC(C)[AlH]C(C)C CDHICTNQMQYRSM-UHFFFAOYSA-N 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
235000014632 disordered eating Nutrition 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
208000024732 dysthymic disease Diseases 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
229960003699 evans blue Drugs 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 1
239000004312 hexamethylene tetramine Substances 0.000 description 1
235000010299 hexamethylene tetramine Nutrition 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
230000007365 immunoregulation Effects 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000007917 intracranial administration Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical group C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000003140 lateral ventricle Anatomy 0.000 description 1
GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
108010052968 leupeptin Proteins 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
229940126601 medicinal product Drugs 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
206010027175 memory impairment Diseases 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
RDOXTESZEPMUJZ-UHFFFAOYSA-N methyl phenyl ether Natural products COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
108010030017 midkine receptors Proteins 0.000 description 1
239000012046 mixed solvent Substances 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
229960005181 morphine Drugs 0.000 description 1
229950006238 nadide Drugs 0.000 description 1
230000008693 nausea Effects 0.000 description 1
230000010807 negative regulation of binding Effects 0.000 description 1
230000008764 nerve damage Effects 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
208000021722 neuropathic pain Diseases 0.000 description 1
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
239000008203 oral pharmaceutical composition Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002902 organometallic compounds Chemical class 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
208000019906 panic disease Diseases 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006072 paste Substances 0.000 description 1
230000007310 pathophysiology Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
BWSDNRQVTFZQQD-AYVHNPTNSA-N phosphoramidon Chemical compound O([P@@](O)(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC=1[C]2C=CC=CC2=NC=1)C(O)=O)[C@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@@H]1O BWSDNRQVTFZQQD-AYVHNPTNSA-N 0.000 description 1
108010072906 phosphoramidon Proteins 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
208000028173 post-traumatic stress disease Diseases 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
239000008057 potassium phosphate buffer Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000000047 product Substances 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000005855 radiation Effects 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
238000003259 recombinant expression Methods 0.000 description 1
230000011514 reflex Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
229950005741 rolipram Drugs 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
210000003625 skull Anatomy 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
229960001790 sodium citrate Drugs 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000003890 substance P antagonist Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
108700012359 toxins Proteins 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
208000027491 vestibular disease Diseases 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Pulmonology (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Immunology (AREA)
Urology & Nephrology (AREA)
Dermatology (AREA)
Cardiology (AREA)
Rheumatology (AREA)
Heart & Thoracic Surgery (AREA)
Reproductive Health (AREA)
Endocrinology (AREA)
Hospice & Palliative Care (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Vascular Medicine (AREA)
Gynecology & Obstetrics (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Otolaryngology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)

UA2000042374A 1997-11-19 1998-10-26 Сполуки піперидиніламінометильних трифлуорометильних циклічних етерів, фармацевтична композиція (варіанти) та спосіб лікування (варіанти) UA59417C2 (uk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IB9701466		1997-11-19
PCT/IB1998/001704 WO1999025714A1 (fr)	1997-11-19	1998-10-26	Composes ether cycliques du type piperidinylaminomethyltrifluoromethyle em tant qu'antagonistes de la substance p

Publications (1)

Publication Number	Publication Date
UA59417C2 true UA59417C2 (uk)	2003-09-15

Family

ID=11004634

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2000042374A UA59417C2 (uk)	1997-11-19	1998-10-26	Сполуки піперидиніламінометильних трифлуорометильних циклічних етерів, фармацевтична композиція (варіанти) та спосіб лікування (варіанти)

Country Status (39)

Country	Link
US (2)	US20030208079A1 (fr)
EP (1)	EP1032571B1 (fr)
JP (2)	JP3394239B2 (fr)
KR (1)	KR100366902B1 (fr)
CN (1)	CN1173974C (fr)
AP (1)	AP909A (fr)
AR (1)	AR016422A1 (fr)
AT (1)	ATE219078T1 (fr)
AU (1)	AU734218B2 (fr)
BG (1)	BG63969B1 (fr)
CA (1)	CA2310627C (fr)
CO (1)	CO4771153A1 (fr)
CZ (1)	CZ297315B6 (fr)
DE (1)	DE69806045T2 (fr)
DK (1)	DK1032571T3 (fr)
DZ (1)	DZ2655A1 (fr)
EA (1)	EA002621B1 (fr)
ES (1)	ES2177058T3 (fr)
HR (1)	HRP20000313B1 (fr)
HU (1)	HUP0101112A3 (fr)
ID (1)	ID24240A (fr)
IL (1)	IL135631A0 (fr)
IS (1)	IS2202B (fr)
MA (1)	MA26567A1 (fr)
MY (1)	MY120558A (fr)
NO (2)	NO20002544L (fr)
NZ (1)	NZ503912A (fr)
OA (1)	OA11380A (fr)
PA (1)	PA8463001A1 (fr)
PE (1)	PE20000021A1 (fr)
PL (1)	PL193484B1 (fr)
PT (1)	PT1032571E (fr)
RS (1)	RS49792B (fr)
SK (1)	SK283460B6 (fr)
TN (1)	TNSN98210A1 (fr)
TR (1)	TR200001463T2 (fr)
TW (1)	TW426667B (fr)
UA (1)	UA59417C2 (fr)
WO (1)	WO1999025714A1 (fr)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9812662D0 (en) *	1998-06-11	1998-08-12	Merck Sharp & Dohme	Therapeutic use
GB9812617D0 (en) *	1998-06-11	1998-08-12	Merck Sharp & Dohme	Therapeutic use
AU3572800A (en) *	1999-05-06	2000-11-21	Pfizer Products Inc.	Substituted benzolactam compounds
RS49964B (sr)	1999-05-17	2008-09-29	Pfizer Products Inc.,	Postupak za dobijanje 2-fenil-3-aminopiridina,njegovih supstituisanih fenil derivata, i njegovih soli
WO2000071538A2 (fr) *	1999-05-21	2000-11-30	Pfizer Products Inc.	Derives 1-trifluoromethyl-4-hydroxy-7-piperidinyl-aminomethylchromane
AU7557000A (en) *	1999-10-07	2001-05-10	Hisamitsu Pharmaceutical Co. Inc.	Piperidine derivatives
ATE257477T1 (de) *	1999-10-18	2004-01-15	Pfizer Prod Inc	Verfahren zur herstellung von zyklischen piperidinylaminomethyl-trifluoromethyl- etherderivaten
JP2001172178A (ja) *	1999-10-25	2001-06-26	Pfizer Prod Inc	偏頭痛治療用のｎｋ−１レセプターアンタゴニスト及びエレトリプタン
IL142810A0 (en) *	2000-05-03	2002-03-10	Pfizer Prod Inc	Pharmaceutical uses for fluoroalkoxybenzylamino derivatives of nitrogen containing heterocycles
US20020049211A1 (en) *	2000-09-06	2002-04-25	Sobolov-Jaynes Susan Beth	Combination treatment for depression and anxiety
EP1192952A3 (fr) *	2000-09-28	2003-03-26	Pfizer Products Inc.	Composition pour le traitement de la dépression et de l'anxieté contenant un antagoniste du recepteur NK-3 et un antagoniste du récepteur NK-1
US6555581B1 (en)	2001-02-15	2003-04-29	Jones Pharma, Inc.	Levothyroxine compositions and methods
BR0207297A (pt)	2001-02-15	2005-04-19	King Pharmaceuticals Inc	Composição farmacêutica em forma sólida e método de preparar uma forma de dosagem sólida de um ingrediente farmaceuticamente ativo
US7101569B2 (en)	2001-08-14	2006-09-05	Franz G Andrew	Methods of administering levothyroxine pharmaceutical compositions
EP1288208B1 (fr)	2001-08-30	2006-07-12	Pfizer Products Inc.	Procedure pour la Preparation du 2-(4-Alkyl-1-Piperazinyl)-Benzaldehyde et derivés du -Benzylidenyl par substitution nucleophilic aromatic du 2-Fluorobenzaldehyde avec le 4-Alkyl-1-Piperazine et de l'eau comme solvant
US20040001895A1 (en) *	2002-06-17	2004-01-01	Pfizer Inc.	Combination treatment for depression and anxiety
WO2004019865A2 (fr) *	2002-08-27	2004-03-11	Witten Mark L	Amelioration des effets de la fumee de cigarette
US6911544B2 (en) *	2002-10-23	2005-06-28	Pfizer Inc.	Process for the preparation of (S,S)-cis-2-phenyl-3-aminopiperidine
US7122700B2 (en)	2004-07-30	2006-10-17	Xerox Corporation	Arylamine processes
DE102008000891A1 (de)	2008-03-31	2009-10-01	Robert Bosch Gmbh	Schutzsystem für Werkzeugmaschinen
DK2729147T3 (en)	2011-07-04	2017-12-18	Irbm - Science Park S P A	NK-1 RECEPTOR ANTAGONISTS FOR TREATMENT OF CORNOVA
US20210015834A1 (en)	2018-02-26	2021-01-21	Ospedale San Raffaele S.R.L.	Nk-1 antagonists for use in the treatment of ocular pain
EP4117673A1 (fr)	2020-03-11	2023-01-18	Ospedale San Raffaele S.r.l.	Traitement d'une déficience en cellules souches

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9317987D0 (en) *	1993-08-26	1993-10-13	Glaxo Group Ltd	Chemical compounds
US5886011A (en) *	1995-03-27	1999-03-23	Hisamitsu Pharmaceutical Co., Inc.	Piperidine derivatives as substance P antagonists
RU2156250C2 (ru) *	1995-04-24	2000-09-20	Новартис Аг	Производные хромона, способ их получения и фармацевтическая композиция
ATE199552T1 (de) *	1995-07-07	2001-03-15	Pfizer	Substituierte benzolaktamverbindungen als substanz-p-antagonisten
TW340842B (en) *	1995-08-24	1998-09-21	Pfizer	Substituted benzylaminopiperidine compounds
US6329396B1 (en) *	1996-06-10	2001-12-11	Pfizer Inc.	Substituted benzylaminopiperidine compounds
WO2000071538A2 (fr) *	1999-05-21	2000-11-30	Pfizer Products Inc.	Derives 1-trifluoromethyl-4-hydroxy-7-piperidinyl-aminomethylchromane
ATE257477T1 (de) *	1999-10-18	2004-01-15	Pfizer Prod Inc	Verfahren zur herstellung von zyklischen piperidinylaminomethyl-trifluoromethyl- etherderivaten

1998
- 1998-10-21 TW TW087117444A patent/TW426667B/zh not_active IP Right Cessation
- 1998-10-26 ES ES98947726T patent/ES2177058T3/es not_active Expired - Lifetime
- 1998-10-26 SK SK723-2000A patent/SK283460B6/sk unknown
- 1998-10-26 ID IDW20000926A patent/ID24240A/id unknown
- 1998-10-26 CN CNB988112930A patent/CN1173974C/zh not_active Expired - Fee Related
- 1998-10-26 AU AU94549/98A patent/AU734218B2/en not_active Ceased
- 1998-10-26 EA EA200000432A patent/EA002621B1/ru not_active IP Right Cessation
- 1998-10-26 IL IL13563198A patent/IL135631A0/xx not_active IP Right Cessation
- 1998-10-26 RS YUP-294/00A patent/RS49792B/sr unknown
- 1998-10-26 HU HU0101112A patent/HUP0101112A3/hu unknown
- 1998-10-26 NZ NZ503912A patent/NZ503912A/xx unknown
- 1998-10-26 DK DK98947726T patent/DK1032571T3/da active
- 1998-10-26 DE DE69806045T patent/DE69806045T2/de not_active Expired - Fee Related
- 1998-10-26 TR TR2000/01463T patent/TR200001463T2/xx unknown
- 1998-10-26 CA CA002310627A patent/CA2310627C/fr not_active Expired - Fee Related
- 1998-10-26 PT PT98947726T patent/PT1032571E/pt unknown
- 1998-10-26 WO PCT/IB1998/001704 patent/WO1999025714A1/fr not_active Ceased
- 1998-10-26 AT AT98947726T patent/ATE219078T1/de not_active IP Right Cessation
- 1998-10-26 JP JP2000521096A patent/JP3394239B2/ja not_active Expired - Fee Related
- 1998-10-26 CZ CZ20001834A patent/CZ297315B6/cs not_active IP Right Cessation
- 1998-10-26 HR HR960576A patent/HRP20000313B1/xx not_active IP Right Cessation
- 1998-10-26 UA UA2000042374A patent/UA59417C2/uk unknown
- 1998-10-26 EP EP98947726A patent/EP1032571B1/fr not_active Expired - Lifetime
- 1998-11-11 PA PA19988463001A patent/PA8463001A1/es unknown
- 1998-11-16 PE PE1998001112A patent/PE20000021A1/es not_active Application Discontinuation
- 1998-11-17 AR ARP980105829A patent/AR016422A1/es unknown
- 1998-11-17 MA MA25354A patent/MA26567A1/fr unknown
- 1998-11-17 MY MYPI98005209A patent/MY120558A/en unknown
- 1998-11-18 DZ DZ980265A patent/DZ2655A1/fr active
- 1998-11-18 TN TNTNSN98210A patent/TNSN98210A1/fr unknown
- 1998-11-18 CO CO98067902A patent/CO4771153A1/es unknown
- 1998-11-19 AP APAP/P/1998/001402A patent/AP909A/en active
2000
- 2000-04-26 IS IS5470A patent/IS2202B/is unknown
- 2000-05-12 OA OA1200000138A patent/OA11380A/en unknown
- 2000-05-15 BG BG104437A patent/BG63969B1/bg unknown
- 2000-05-18 NO NO20002544A patent/NO20002544L/no not_active Application Discontinuation
- 2000-05-18 KR KR10-2000-7005431A patent/KR100366902B1/ko not_active Expired - Fee Related
- 2000-05-18 PL PL98340642A patent/PL193484B1/pl unknown
2002
- 2002-06-18 JP JP2002177452A patent/JP2003040777A/ja active Pending
2003
- 2003-04-21 US US10/419,425 patent/US20030208079A1/en not_active Abandoned
2004
- 2004-07-07 NO NO20042879A patent/NO20042879L/no not_active Application Discontinuation
- 2004-11-18 US US10/991,977 patent/US20050171354A1/en not_active Abandoned

Also Published As

Publication number	Publication date
BG104437A (en)	2001-02-28
PA8463001A1 (es)	2000-09-29
DZ2655A1 (fr)	2003-03-22
PE20000021A1 (es)	2000-02-25
US20050171354A1 (en)	2005-08-04
DE69806045D1 (en)	2002-07-18
ES2177058T3 (es)	2002-12-01
CN1173974C (zh)	2004-11-03
RS49792B (sr)	2008-06-05
AP909A (en)	2000-12-04
SK7232000A3 (en)	2001-09-11
DE69806045T2 (de)	2002-11-14
NZ503912A (en)	2002-09-27
JP2001523680A (ja)	2001-11-27
US20030208079A1 (en)	2003-11-06
AU9454998A (en)	1999-06-07
HRP20000313B1 (en)	2002-04-30
KR100366902B1 (ko)	2003-01-09
CN1279681A (zh)	2001-01-10
JP2003040777A (ja)	2003-02-13
AU734218B2 (en)	2001-06-07
SK283460B6 (sk)	2003-08-05
PL193484B1 (pl)	2007-02-28
YU29400A (sh)	2003-02-28
DK1032571T3 (da)	2002-07-15
AP9801402A0 (en)	1998-12-31
PT1032571E (pt)	2002-09-30
MA26567A1 (fr)	2004-12-20
EA200000432A1 (ru)	2000-12-25
NO20002544L (no)	2000-07-17
CZ20001834A3 (cs)	2001-07-11
HUP0101112A3 (en)	2002-06-28
AR016422A1 (es)	2001-07-04
NO20042879L (no)	2000-07-17
CA2310627A1 (fr)	1999-05-27
HUP0101112A2 (hu)	2002-05-29
IS2202B (is)	2007-02-15
ATE219078T1 (de)	2002-06-15
ID24240A (id)	2000-07-13
CO4771153A1 (es)	1999-04-30
WO1999025714A1 (fr)	1999-05-27
EA002621B1 (ru)	2002-06-27
JP3394239B2 (ja)	2003-04-07
TW426667B (en)	2001-03-21
OA11380A (en)	2004-01-27
TR200001463T2 (tr)	2000-12-21
MY120558A (en)	2005-11-30
EP1032571A1 (fr)	2000-09-06
TNSN98210A1 (fr)	2005-03-15
IL135631A0 (en)	2001-05-20
IS5470A (is)	2000-04-26
PL340642A1 (en)	2001-02-12
CA2310627C (fr)	2005-08-09
BG63969B1 (bg)	2003-08-29
HK1033313A1 (en)	2001-08-24
EP1032571B1 (fr)	2002-06-12
HRP20000313A2 (en)	2000-12-31
CZ297315B6 (cs)	2006-11-15
NO20002544D0 (no)	2000-05-18

Publication	Publication Date	Title
UA59417C2 (uk)	2003-09-15	Сполуки піперидиніламінометильних трифлуорометильних циклічних етерів, фармацевтична композиція (варіанти) та спосіб лікування (варіанти)
JP2500279B2 (ja)	1996-05-29	アザ二環式化合物、これを含有する医薬組成物及び治療のための使用方法
EP0591333B1 (fr)	1997-03-05	Derives d'azanorbornane
US6180647B1 (en)	2001-01-30	Substituted benzolactam compounds as substance P antagonists
US5688806A (en)	1997-11-18	Spiroazacyclic derivatives as substance P antagonists
NZ308207A (en)	1998-07-28	Substituted benzylaminophenylpiperidine derivatives
PL172069B1 (pl)	1997-07-31	Sposób wytwarzania nowych pochodnych podstawionej 3-aminochinuklidyny PL PL PL PL PL
JP2023545046A (ja)	2023-10-26	アルファ－ｄ－ガラクトピラノシドのスピロ誘導体
WO2006035303A1 (fr)	2006-04-06	Antagonistes de recepteurs muscariniques
DE69430074T2 (de)	2002-09-05	Analgetische 4-arylisoindolen
US6288225B1 (en)	2001-09-11	Substituted benzolactam compounds as substance P antagonists
US5972930A (en)	1999-10-26	Pyridinylamino tricyclic compounds as substance P antagonists
MXPA00004889A (en)	2001-07-09	Piperidinylaminomethyl trifluoromethyl cyclic ether compounds as substance p antagonists